Process of acetylating triethyl citrate



Patented 'July 27, 1948 j chooses-F "AGE'IYLATING TRIETHYL- 1 CI-TRATE Gharles H; FisheraA bington, Pa., and Martin I-m' Fein, Riverside; N; J.

, assignors to the United StatesgofcAmenioa as. represented by the Secretaryrof Agriculture.

Nam-twist: ppli Match-21,1946" t l. serja1-No.fi56J 1 015ml. (01. zoos-484i (Granted under the act of March 3,, 1883;. as: s l i 1 l v t amended April 30,

This application is made under the actof March 3c fi3ta e r r iio Ap 1130? 928 and [the invention herein described ii patented, may-be manufactured and used byor for the Government,ofi lthe-Unitedstatesof Americaiior governmental. purposes withoutlthelpayrnent to of. any royaltytthereonl 3 I v v I t The present invention relates. to an improved processfoigacylating esters of hydroxyacids, such, asalkylslactates and; particularlyto a process of acyl ating such. hydroxy esters continuously. It isrlinown that. esters of hydroxyta-cldscan'be preparediby treatment with. acid anhydrid'es, acid. chlorides; and. ketene. However, when accom plishe'dlby; the'procedures of previous investiga tors, the acylationfl-of hydroxy esters has beentedious and time-consuming. Previous methods. have, not been [simple enough} that continuous operationrislfeasible. i s l s y v We have found that the procedures usedjin'previous investigations can be simplified in such a manner that time and materials areisave'd. More: over, We have found that cooling isnot'necessary whenthe acylating agent is added to the'alk'ylester of hydrox-yacid.- Moreover, we liave r0unu thattit isnottnecessary or advantageouslto allow the-reactionmixture to stand forsome-timeprion todistillation. The discovery that the acyl'ation. can be made to occur rapidly is of practicalimpor tance since, under these conditions, the acylation can be operated advantageously as a continuous process-in industry. 1 Q

"Although. satisfactory for the: preparation-1 of. smalllquantities of methyl alphaacetoxypropi0,-- nate in the ,laboratory, the methods 1 described by previous workers have not been satisfactory for continuous operation where low contact times are-"desirable. it Other disadvantages of previous methods will become apparent from comparing previous methods with those of thepresent'invention. l ,l i Our invention is illustrated by,. hut not limited to,,thefollowingtexamples:

Example I One drop of concentrated sulfuric acid was addedrtora mixtureofl 156- g; methyl lactate; 169" g. acetic; anhydride: (approximately IO-percent. in excesszloi:thettheo'retioah amount) and-150 cc. of diphenyl ether. The temperatureirose:immedi-t ately to about 100 C. The mixture l was allqwed; to: stand forJlSiminutes and t thenswas distilled} thr a 12- n h Widmer cqlmnnv J ai re m consisted mainly of acetic aoidt; 'Fhhe desired proda 1928'; 3705102 G'.,' 757) s l v v 2 l v i uot, methyl alphaacetoxypropionate; distilled principally atil'lz to 173% The traction collected at l68to 173 amountedto-Zllg. (Qtipereent of; a refractive index of the theoretical) and-had M091 at 120 C.

The diphenyl ether, which was used; to drive over all the methyl -acetoxypropi onate, remained= in the distillingfiask It wasiused in'subsequent m preparations of methyl acetoxypropionate.

Ex mple 1 Methyl lactate-(156a) 169g. acetic anhydride, and: 40 cc; diphenyl ether were mixed and distllledzimmediat'ely through a l2-inch Widmer col-* umn. Acetic acidxand 2l-1 -g. (96lpercent of the theoretical yield) or methyl alpha-acetoxypro pionatezilwereobtained. Refractive index" of the product at .20 C. was 1.4089.

Example; I II A mintureof' I69 acetic anhydride and 1 drop of concentrated sulfuric acidgwas addedgradu'ally.

from, a separatoryfunnelto 156"" g. ofTmethyL lactate. During the addition, the reaction temperature rose to 95 C. Diphenyl ether 50 cc.)

was added; and the mixtureiwas distilled in vacuum; The yield oflmeth'yl" alpha-acet'oxyprm pionate boiling at 76 Cfunder 20mm. of meroury pressure was 96.4 percent ofthethe'oretical.

Etcample I V V Methyldactate (8321s. or 8 moles) was added from-saqseparatory funnel to a mixture f of 857 s.

(8A moles) of acetic anhydride and-019 gt con centratedzl sulfuric acid contained in la :fiask v pro videdtwith a mechanical stirrer; theflask was i mmers'ed in a water bath: During the additlon of methyl lactate, the reaction temperature was kept at approximately GG 'C'. hyaddition of suitable amounts of. ice to the Waterbath; Distillation of thewreaction mixtureyielded"1109.5;g, (94.-9;:per-" centofithetheoretical) ofmethylalpha:acetoxy propionate, most of which distilled zttfili v tact? Us at? underwlitsmm. of: mercury pressure it v Example VI mixture was distilled at atmospheric pressure.

The yield of methyl alpha-acetoxypropionate was 94 percent of the theoretical. 7

Example VII A mixture of 2 moles (208 g.) of methyl lactate and 2- moles (204 g.) of acetic anhydride was passed through a preheater at a controlled rate and into continuous distillation apparatus. The apparatus was arranged for accurate temperature control of the preheater, column sections, and still pot. The material to be distilled, after'being passed through the preheater, was allowed to enter at a point approximately two-fifths of the total length from the bottom of the column. The lower portion of the column and still pot were kept at temperature near the boiling point (172 C.) of methyl alpha-acetoxypropionate. The upper portion of the column and still-head were controlled in such a manner that acetic acid distilled over. The desired product, methyl alphaacetoxypropionate, was removed from the small still pot through a side arm and appropriate siphoning arrangement. Purity of the product was checked by index of refraction at fixed intervals. The overall height of the column used was approximately 6 feet, the preheater capacity was about ml., the column diameter was approxi-v mately V inch, the upper column was packed with small Berl saddles, and the lower column had Vigreux-type indentations. The still pot capacity was 100 ml. (This equipment is described also in Industrial and Engineering Chemistry, vol. 36, March 1944, pp. 235-238.)

Under proper adjustment of rate of addition of material through the preheater and temperature control of the column, material of high purity can be made continuously with high conversions.

Material of high purity can be made in high yields at both faster or slower feed rates, as Well as at higher or lower preheater temperatures, than those indicated below:

Preheater Contact time Feed rate temperature in preheater Cc./min. C. Min.

Example VIII A mixture, in molecular proportion, of isobutyl. glycolate (isobutyl hydroxyacetate) and propionic anhydride was treated in essentially the same manner as described under Example VIII. Minor changes in temperature control were required due;

to different boiling points of materials to be reacted and separated. The only change in apparatus was the replacement of the Vigreux section of the distillation column by a section packed with Berl saddles 4 inch). The products removed continuously from the apparatus were propionic acid (distillate) and isobutyl acetoxyacetate (from the still pot) Redistilled isobutyl acetoxyacetate: (B. P.=96 C./8 mm. (mercury), 80.5 C./3.2 mm.

(mercury); N =1.4l93.)

Still-head temperature C 139-141 Upper column temperature C 140-143 Lower column temperature C 198-206 Still-"pot temperature C 218-224 Preheater temperature C 123-126 Feed rate into preheater.. cc./minute Approx. 6

Ercample X Acetic anhydride containing a small amount of concentrated sulfuric acid (several drops per mole) was fed into a mixing chamber simultaneously' with methyl alpha hydroxyisobu-tyrate. Prior topassage by gravity into the mixing chamber; each was stored in a 1000 ml. burette. The

' two burettes and the mixing chamber were under the same pressure, this pressure being used to transfer the material from the mixing chamber through the preheater into the distillation unit.

With proper manipulation of stop-cocks and 7o ally no lower boiling material distilled-during.- the recycling process. I

Feed rate into preheater cc./minute V 20 Still-pot temperature C.. 210-235 Distillate temperature C.. 117

Preheater temperature ..C

- pinch-clamps, it was possible to replenish continuously the burettes with the reactants and also feed the reactor and still continuously. Acetic anhydride and methyl alpha-hydroxyisobutyrate" were reacted in essentially molecular proportions.

' The apparatus was the same as describedunder Example IX except for the addition of the burettes for simultaneous introduction of reactants. The operation of the apparatus was the same as described under Example VIII, the only changes being described above. 7 Feed rate into preheater cc./minute 10 Still -head temperature C 1 15 Still-pot temperature C -170 Preheater temperature C. 89-115 -The products were: methyl alpha-acetoxyisobutyrate (B. P. 170.5 (atm.), N 1.4137) withdrawn from the still-pot and acetic acid distilled from the column.

' Example x1 Castor oil (glyceryl triricinoleate) was reacted continuously with acetic anhydride and the products continuously separated, using the procedure Triethyl citrate was reacted continuously wit acetic anhydride and the products continuously separated, using the procedure and apparatus described under Example X. Acetylated triethylcitrate removed from the still-pot was passed through the preheater and column again to insure removal of all low-boiling material. Virtu- Although our invention is specifically illustrated by the above examples, it is understood that it is not limited to the particular materials or procedures disclosed. The general applicability of our invention to the production of esters of hydroxy acids will readily be seen by those skilled in the art. The above processes are applied to esters of other hydroxy acids, such as malic acid and tartaric acid.

It will be apparent to those skilled in the art that various modifications of procedure may be employed without departing from the scope of our invention. For example, the reactants may be passed directly into a continuous still without first being passed through a preheater. Moreover, another liquid, such as benzene and toluene, may be used with the reactants to facilitate distillation of the carboxylic acid. Bases such as pyridine or various acids may be added with the reagents because of their catalytic action. Smaller or larger proportions of the acid anhydride may be used. The time of preheating can be lengthened and the temperature raised without adverse effects. Subor super-atmospheric pressures may be used. Lower pressures are particularly useful when anhydrides of higher acids are used. The acylation can be carried out continuously, the products stored, and distilled later if desired. The acylation may be carried out continuously, and the resulting material used without distillation in subsequent operation, such as pyrolysis, if desired. If desired, an alkaline catalyst can be used in one of 210 to 235 C., continuously distilling the reaction mixture of said ester and a'nhydride, maintaining the upper part of the still at such tem-' perature that acetic acid distills off, the acetylated citric acid ester collecting in the still.

CHARLES H. FISHER. MARTIN L.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,367,798 Rehberg et al. Jan. 23, 1945 2,374,428 Fisher et a1 Apr. 124, 1945 OTHER REFERENCES Fein et al., Incl.'& Eng. Chem." vol. v36 (1944) pp. 235-238. 

